Red wine and/or exercise – your choice

Deteriorating brain function is the bane of getting old. The most severe and debilitating form of cognitive decline is the development of dementia, a collective term used to describe various symptoms of cognitive decline, such as forgetfulness. The estimated proportion of the general population aged 60 and over with dementia at a given time is between 5-8%.

Dementia is not a single disease in itself, but a general term to describe symptoms of impairment in memory, communication, and thinking. Although it mostly affects older people, it is not necessarily a normal part of ageing as it can be influenced by lifestyle factors.

Boosting brain function

Sure, a regular glass of red wine has been shown to have the ability to improve cognitive function as we age. We covered this in detail in a previous blog. But so does regular exercise. Exercise has a broad range of beneficial healthful effects.

A new study published on 9 July 2020 tested the hypothesis that it might be possible to reverse brain ageing through systemic interventions such as exercise. The scientists from the University of California tested whether the beneficial effects of exercise on cognition in aged mice could be transferred in plasma from one mouse to another. Indeed, plasma from young or old mice that had exercised when transferred to other aged mice showed beneficial effects in their brains even if they had not exercised.

How is this possible?

To discover what specific biological factors in the blood might be behind these effects, the amounts of different soluble proteins in the blood of active versus sedentary mice were measured. After some intensive search, the scientists identified the enzyme glycosylphosphatidylinositol-specific phospholipase D1 (Gpld1) as a factor in plasma that might mediate this favourable effect.

Gpld1 is produced by the liver. The team found that Gpld1 increases in the blood circulation of mice following exercise, and that Gpld1 levels correlate closely with improvements in the animals’ cognitive performance.

And not only in rats!

Analysis of previously collected human data showed that Gpld1 is also elevated in the blood of healthy, active elderly adults compared to less active elders.

To test whether Gpld1 itself could drive the observed benefits of exercise, the researchers used genetic engineering to coax the livers of aged mice to produce extra Gpld1, and measured various aspects of cognition and memory. They found that three weeks of the treatment produced similar beneficial cognitive effects as six weeks of regular exercise.

The scientists are now working to better understand precisely how Gpld1 interacts with other biochemical signalling systems to produce its brain-boosting effects (as it doesn’t pass the blood/brain barrier). The hope is to be able to identify specific targets for a future food supplement with Gpld1 that could one day confer many of the protective benefits of exercise for the frail.

So what’s your choice?

So now there is a choice, red wine or exercise or maybe both to retain good cognitive function.

But the question is how much exercise is needed to get the optimal benefit. Would the recommended 10,000 steps a day be sufficient and would a glass of red wine add to the benefit?

Or, horror, would the liver be too busy to metabolise the alcohol from the red wine to have time to also produce the Gpld1?

I want to know more!

The complexity of weight gain

No fatness gene found.

New fatness gene found.

They have found the culprit, the fatness gene. So all we need now is a bit of gene therapy, or not. Still feel hungry? Well, there is an explanation for that as well. Or is it the carbohydrates that are responsible for the explosion of obesity. According to the latest diet advice you should avoid all kinds of carbs, but eat as much fat as you like. Previously it was the fat to avoid, with a proliferation of low-fat products that now seem redundant. But the Coca-Cola Company and its ilk wouldn’t give up their sugary drinks that easily. They have enlisted a number of fitness experts to promote exercise as the solution. Sounds complex? Well, that is because it is. Let’s look at the ideas one at a time.

Hunger

We have to start with hunger. Have you ever heard of the AGRP neurons? I guess not, but if you’re often hungry you can blame hunger-sensitive cells in your brain known as AGRP neurons. These neurons are responsible for the unpleasant feelings of hunger making sure that you look for food when your energy level is low, even if you don’t want to. They seem to be an evolutionary part of a motivational system to encourage ancient humans to seek food or water despite having to venture into dangerous environments to do so. Their signals should really be redundant now when food is readily available, but they remain, making it a struggle to maintain a restricted diet and lose weight.

In earlier studies, researchers found that other neurons that promoted eating did so by increasing positive feelings associated with food. In other words hunger makes food taste better, which seems natural. On the contrary the AGRP neurons produce negative feelings. Surprisingly, research results using mice showed that they did not actually have to eat to quiet the AGRP neurons. Instead, the cells ceased activity as soon as an animal saw food or even an artificial signal that predicted food. And their activity remained low while the animal was eating.

If you think that you can just look at food to relieve hunger pangs, think again. Unfortunately, other neurons will make sure that you also eat the food. So no luck there.

Fatness gene

Moving on from the brain to the genome. Scientists have previously found over 100 regions on the human genome that correlate with obesity, likely through regulating the brain’s perception of hunger (here we go again) and the distribution of fat throughout the body. Now scientists at the University of British Columbia have discovered a gene that directly controls the production of fat cells and the growth of those cells, which are precursors to obesity.

The gene can be found in every cell of the body and encodes a protein called 14-3-3zeta. Silencing the gene in mice resulted in a 50 per cent reduction in the amount of unhealthy white fat that is associated with obesity, heart disease and diabetes. And this was despite the mice consuming the same amount of food. The scientists not only identified zeta as the operative protein, but demonstrated a clear cause-and-effect between 14-3-3zeta and fat accumulation.

We get fatter through the multiplication of our fat cells, and through the growth of individual fat cells. And the zeta protein affects both the number of cells and play a role in the growth cycle of these cells. Early days yet, but scientists speculate that there could be possible to suppress the gene or to develop a drug that could block the protein and thus prevent fat accumulation in people who are on their way to become overweight.

But there is a large gap between theory and practice, so no luck yet.

Fat and carbs

Low-fat food popularity (Photo: Barry Ennor).

Low-fat food gained popularity (Photo: Barry Ennor).

So what can you do now? Let’s look at the two individual components of the diet that have been associated with weight gain. A lot of people have very strong opinions about what matters for weight gain, as we have covered before. First it was fat as it seems natural to associate fat consumption with fat accumulation. And fat also provides double the energy per weight compared to the other macro nutrients. Thus industry developed a number of low-fat products to entice consumers. However, they still wanted the products to taste good so in many cases they increased the sugar content and thus energy intake. Such products have been popular for quite some time, but our metabolism is complex so in reality people didn’t really lose weight. Out came the carbohydrate theory, proposing instead that it was carbs that made us fat and not fat in the diet. So fat became free for all but carbohydrate-rich sources like bread, pasta and potatoes should be limited as much as possible. And people on such diets actually lost weight.

So is it proven? Hold on, not so fast. A new study from the US National Institutes of Health presents some of the most precise human data yet on whether cutting carbs or fat has the most benefits for losing body fat. And the researchers show how, contrary to popular claims, restricting dietary fat can lead to greater body fat loss than carb restriction, even though a low-carb diet reduces insulin and increases fat burning.

Despite authoritative claims about carbohydrate versus fat restriction for weight loss, nobody had ever measured in detail what would happen if carbs were selectively cut from the diet while fat remained at a baseline or vice versa. Studying the effects of diet on weight loss is often confounded by the difficulty in measuring what people actually eat. To counter this, 19 consenting adults with obesity were confined to a metabolic ward for a pair of 2-week periods, over the course of which every bit of food eaten was closely monitored and controlled. During the first period, 30 per cent of baseline calories were cut through carb restriction alone, while fat intake remained the same. During the second period the conditions were reversed.

At the end of the experiment body fat lost with dietary fat restriction was greater compared with carbohydrate restriction, even though more fat was burned with the low-carb diet. However, over prolonged periods the model predicted that the body acts to minimize body fat differences between diets that are equal in calories but varying widely in their ratio of carbohydrate to fat. So the conclusion is that although not all calories are created equal when it comes to body fat loss, over the long term, it’s pretty close.

So feel free to limit energy intake the way you feel most comfortable with, as long as it is consistent over time.

Exercise

Exercise not enough to reduce weight (Photo: Sangudo).

Exercise not enough to reduce weight (Photo: Sangudo).

The remaining part of the energy equation is energy expenditure. Coca-Cola, the world’s largest producer of sugary beverages, is backing a new “science-based” solution to the obesity crisis: Exercise more and worry less about cutting calories to maintain a healthy weight.

The beverage giant provides support to a new nonprofit organization called the Global Energy Balance Network with a team of influential scientists who are promoting the message in medical journals, at conferences and through social media. And the message:  Weight-conscious consumers are overly fixated on how much they eat and drink while not paying enough attention to exercise.

This message has not been uncontested with health experts saying it is misleading and an effort to deflect criticism about the role sugary drinks have played in the spread of obesity and Type 2 diabetes. It is clear that exercise has only minimal impact on weight compared with what people consume. A food industry critic, professor Marion Nestle, is especially blunt in her comments: The Global Energy Balance Network is nothing but a front group for Coca-Cola. Coca-Cola’s agenda here is very clear. Get these researchers to confuse the science and deflect attention from dietary intake.

While people can lose weight in several ways, many studies suggest that those who keep it off for good consume fewer calories. Growing evidence also suggests that maintaining weight loss is easier when people limit their intake of high glycemic foods such as sugary drinks and other refined carbohydrates, which sharply raise blood sugar.

So what to do?

There is nothing much you can do yet about the genes you have inherited from your parents. But you can make sure that you eat a nutrient dense diet rather that an energy dense diet, and reduce overall energy intake in a way you feel comfortable with. As scientists say about their studies, rubbish in, rubbish out, or in this case junk food in, belt out. Physical activity is important and certainly helps. But studies show that exercise increases appetite, causing people to consume more calories. Exercise also expends far fewer calories than most people think. And to compensate the fluid loss with an energy drink at the end of the exercise completely defeats the purpose.

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